Exploring the therapeutic potential of Aloin: unraveling neuroprotective and anticancer mechanisms, and strategies for enhanced stability and delivery.

We investigate the therapeutic potential of Aloin A and Aloin B, two natural compounds derived from Aloe vera leaves, focusing on their neuroprotective and anticancer properties. The structural differences between these two epimers suggest that they may exhibit distinct pharmacological properties. Our investigations revealed that both epimers are not stable in aqueous solution and tend to degrade rapidly, with their concentration decreasing by over 50% within approximately 12 h. These results underscore the importance of addressing issues such as the need for encapsulation into effective drug delivery systems to enhance stability. ThT fluorescence experiments showed that neither compound was able to inhibit Aß amyloid aggregation, indicating that other mechanisms may be responsible for their neuroprotective effects. Next, an equimolar mixture of Aloin A and Aloin B demonstrated an ability to inhibit proteasome in tube tests, which is suggestive of potential anticancer properties, in accordance with antiproliferative effects observed in neuroblastoma SH-SY5Y and HeLa cell lines. Higher water stability and increased antiproliferative activity were observed by encapsulation in carbon dot nanoparticles, suggesting a promising potential for further in vivo studies.

Magnetic-stirring-enhanced mechanical amorphous dispersion extraction for the hydrophobic phytochemical constituents using an aqueous solution from a medicinal plant.

A method involving chitosan-assisted magnetic-stirring-enhanced mechanical amorphous dispersion extraction was developed and utilized to extract hydrophobic anthraquinones from Rhei Radix et Rhizoma prior to ultrahigh performance liquid chromatography analysis. Incorporating natural chitosan as a dispersant facilitated the extraction of hydrophobic anthraquinones using purified water, considerably enhancing the eco-friendliness of the extraction methodology. To optimize extraction efficiency, an extensive evaluation of the crucial parameters influencing rhubarb yield was conducted. Furthermore, a response surface methodology was applied to optimize the extraction conditions. Under these optimized conditions, the method exhibited linearity ranges of 0.1-100 µg/mL, with correlation coefficients between 0.9990 and 0.9998. The method's intraday (n = 6) and interday (n = 6) precision levels were maintained at ≤3.58%, which was considered to be within acceptable limits. The computed detection and quantification limits were 16.54-24.60 and 54.91-82.04 ng/mL, respectively. Consequently, this optimized method was effectively employed to extract five specific compounds (aloe-emodin, emodin, rhein, chrysophanol, and physcion) from Rhei Radix et Rhizoma, achieving recoveries ranging from 86.43% to 102.75%.

Natural Sunlight-Mediated Emodin Photoinactivation of Aeromonas hydrophila.

Aeromonas hydrophila can be a substantial concern, as it causes various diseases in aquaculture. An effective and green method for inhibiting A. hydrophila is urgently required. Emodin, a naturally occurring anthraquinone compound, was exploited as a photo-antimicrobial agent against A. hydrophila. At the minimum inhibitory concentration of emodin (256 mg/L) to inactivate A. hydrophilia in 30 min, an 11.32% survival rate was observed under 45 W white compact fluorescent light irradiation. In addition, the antibacterial activity under natural sunlight (0.78%) indicated its potential for practical application. Morphological observations demonstrated that the cell walls and membranes of A. hydrophila were susceptible to damage by emodin when exposed to light irradiation. More importantly, the photoinactivation of A. hydrophila was predominantly attributed to the hydroxyl radicals and superoxide radicals produced by emodin, according to the trapping experiment and electron spin resonance spectroscopy. Finally, a light-dependent reactive oxygen species punching mechanism of emodin to photoinactivate A. hydrophila was proposed. This study highlights the potential use of emodin in sunlight-mediated applications for bacterial control, thereby providing new possibilities for the use of Chinese herbal medicine in aquatic diseases prevention.

Elucidation of inhibitory effects of bioactive anthraquinones towards formation of DNA advanced glycation end products (DNA-AGEs).

DNA is essential in biological processes as it directs transcription and translation assisting in RNA and protein synthesis. Extended periods of elevated blood glucose levels cause non-enzymatic DNA glycation, which results in the formation of DNA-AGEs and the production of free radicals, causing structural perturbation of DNA. In this work, we have investigated the glycation of calf thymus (ct-DNA) DNA and examined its inhibition by two anthraquinone derivatives, purpurin and aloin. Ribose sugar served as the glycating agent inducing non-enzymatic glycation of DNA and subsequent DNA-AGEs formation. UV-vis and fluorescence spectroscopic methods were utilized to characterize DNA-AGE formation in vitro. Circular dichroism (CD) spectroscopy was used to observe the structural disruption of DNA caused by glycation. The changes in AGEs fluorescence intensity and melting temperature (Tm) were measured to assess the inhibition of glycation process by aloin and purpurin. These derivatives demonstrated inhibitory effects via binding to glycating sites of ct-DNA or by scavenging free radicals generated during glycation. The current study elucidates the inhibitory actions of aloin and purpurin on DNA glycation, suggesting their possible applications in mitigating the adverse consequences linked to increased ribose concentrations.

Emodin Blocks mPTP Opening and Improves LPS-Induced HMEC-1 Cell Injury by Upregulation of ATP5A1.

BACKGROUND: Emodin has been shown to exert anti-inflammatory and cytoprotective effects. Our study aimed to identify a novel anti-inflammatory mechanism of emodin. METHODS: An LPS-induced model of microvascular endothelial cell (HMEC-1) injury was constructed. Cell proliferation was examined using a CCK-8 assay. The effects of emodin on reactive oxygen species (ROS), cell migration, the mitochondrial membrane potential (MMP), and the opening of the mitochondrial permeability transition pore (mPTP) were evaluated. Actin-Tracker Green was used to examine the relationship between cell microfilament reconstruction and ATP5A1 expression. The effects of emodin on the expression of ATP5A1, NALP3, and TNF-α were determined. After treatment with emodin, ATP5A1 and inflammatory factors (TNF-α, IL-1, IL-6, IL-13 and IL-18) were examined by Western blotting. RESULTS: Emodin significantly increased HMEC-1 cell proliferation and migration, inhibited the production of ROS, increased the mitochondrial membrane potential, and blocked the opening of the mPTP. Moreover, emodin could increase ATP5A1 expression, ameliorate cell microfilament remodeling, and decrease the expression of inflammatory factors. In addition, when ATP5A1 was overexpressed, the regulatory effect of emodin on inflammatory factors was not significant. CONCLUSION: Our findings suggest that emodin can protect HMEC-1 cells against inflammatory injury. This process is modulated by the expression of ATP5A1.

The Role of Emodin in the Treatment of Bladder Cancer Based on Network Pharmacology and Experimental Verification.

BACKGROUND AND PURPOSE: Emodin, a compound derived from rhubarb and various traditional Chinese medicines, exhibits a range of pharmacological actions, including antiinflammatory, antiviral, and anticancer properties. Nevertheless, its pharmacological impact on bladder cancer (BLCA) and the underlying mechanism are still unclear. This research aimed to analyze the pharmacological mechanisms of Emodin against BLCA using network pharmacology analysis and experimental verification. METHODS: Initially, network pharmacology was employed to identify core targets and associated pathways affected by Emodin in bladder cancer. Subsequently, the expression of key targets in normal bladder tissues and BLCA tissues was assessed by searching the GEPIA and HPA databases. The binding energy between Emodin and key targets was predicted using molecular docking. Furthermore, in vitro experiments were carried out to confirm the predictions made with network pharmacology. RESULTS: Our analysis identified 148 common genes targeted by Emodin and BLCA, with the top ten target genes including TP53, HSP90AA1, EGFR, MYC, CASP3, CDK1, PTPN11, EGF, ESR1, and TNF. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated a significant correlation between Emodin and the PI3KAKT pathway in the context of BLCA. Molecular docking investigations revealed a strong affinity between Emodin and critical target proteins. In vitro experiments demonstrated that Emodin inhibits T24 proliferation, migration, and invasion while inducing cell apoptosis. The findings also indicated that Emodin reduces both PI3K and AKT protein and mRNA expression, suggesting that Emodin may mitigate BLCA by modulating the PI3K-AKT signaling pathway. CONCLUSION: This study integrates network pharmacology with in vitro experimentation to elucidate the potential mechanisms underlying the action of Emodin against BLCA. The results of this research enhance our understanding of the pharmacological mechanisms by which Emodin may be employed in treating BLCA.

Synthesis, Antimicrobial Evaluation, and Interaction of Emodin Alkyl Azoles with DNA and HSA.

OBJECTIVE: This study aimed to overcome the growing antibiotic resistance. Moreover, the new series of emodin alkyl azoles were synthesized. METHOD: The novel emodin alkyl azoles were synthesized using commercial emodin and azoles by alkylation. The NMR and HRMS spectra were employed to confirm the structures of novel prepared compounds. The in vitro antibacterial and antifungal activities of the prepared emodin compounds were studied by the 96-well plate method. The binding behavior between emodin 4-nitro imidazole compound 3c and S. aureus DNA was researched using an ultraviolet-visible spectrophotometer. Furthermore, fluorescence spectrometry was used to explore the interaction with human serum albumin (HSA). RESULTS: The in vitro antimicrobial results displayed that compound 3c gave relatively strong activities with MIC values of 4-16 µg/mL. Notably, this compound exhibited 2-fold more potent activity against S. aureus (MIC = 4 µg/mL) and E. coli (MIC = 8 µg/mL) strains than clinical drug Chloromycin (MIC = 8 and 16 µg/mL). The UV-vis absorption spectroscopy showed that 4-nitro imidazole emodin 3c could form the 3c-DNA complex by intercalating into S. aureus DNA, inhibiting antimicrobial activities. The simulation results displayed that the emodin 3c and DNA complex were formed by hydrogen bonds. The spectral experiment demonstrated that compound 3c could be transported by human serum albumin (HSA) via hydrogen bonds. The molecular simulation found that the hydroxyl group and the nitroimidazole ring of the emodin compound showed an important role in transportation behavior. CONCLUSION: This work may supply useful directions for the exploration of novel antimicrobial agents.

Ultrasound-assisted extraction of emodin from Rheum officinale Baill and its antibacterial mechanism against Streptococcus suis based on CcpA.

Emodin was extracted from Rheum officinale Baill by ultrasound-assisted extraction (UAE), and ethanol was chosen as the suitable solvent through SEM and molecular dynamic simulation. Under the optimum conditions (power 541 W, time 23 min, liquid to material ratio 13:1 mL/g, ethanol concentration 83 %) predicted by RSM, the yield of emodin was 2.18 ± 0.11 mg/g. Moreover, ultrasound power and time displayed the significant effects on the extraction process. Extracting dynamics analysis indicated that the extraction process of emodin by UAE conformed to Fick's second diffusion law. The results of antibacterial experiments suggested that emodin can damage cell membrane and inhibit the expression of cps2A, sao, mrp, epf, neu and the hemolytic activity of S. suis. Biolayer interferometry and FT-IR multi-peak fitting assays demonstrated that emodin induced a secondary conformational shift in CcpA. Molecular docking and molecular dynamics confirmed that emodin bound to CcpA through hydrogen bonding (ALA248, GLU249, GLY129 and ASN196) and π-π T-shaped interaction (TYR225 and TYR130), and the mutation of amino acid residues affected the affinity of CcpA to emodin. Therefore, emodin inhibited the sugar utilization of S. suis through binding to CcpA, and CcpA may be a potential target to inhibit the growth of S. suis.

ß-1,3-d-glucan particles-based "nest" protected co-loaded Rhein and Emodin regulates microbiota and intestinal immunity for ulcerative colitis treatment.

Herein, a ß-1,3-D-glucan based yeast cell wall loaded with co-loaded nanoparticles of Rhein (RH) and Emodin (EMO), was developed for the combined treatment of ulcerative colitis (UC) by modulating gut microbiota and the Th17/Treg cell balance. This was achieved through an oral "nano-in-micro" advanced drug delivery system. Specifically, RH was grafted onto the HA chain via disulfide bonds to synthesize a reduction-sensitive carrier material and then used to encapsulate EMO to form nanoparticles with a specific drug ratio (denoted as HA-RH/EMO NPs). As anticipated, HA-RH/EMO NPs were encased within the "nests"-yeast cell wall microparticles (YPs), efficiently reach the colon and then released gradually, this occurs mainly due to the degradation of ß-1,3-D-glucan by ß-glucanase. Additionally, HA-RH/EMO NPs demonstrated a significant reduction-sensitive effect in GSH stimulation evaluations and a remarkable ability to target macrophages in in vitro cell uptake studies. Notably, HA-RH/EMO NYPs reduced inflammatory responses by inhibiting the PI3K/Akt signaling pathway. Even more crucially, the oral delivery and drug combination methods significantly enhanced the regulatory effects of HA-RH/EMO NYPs on gut microbiota and the Th17/Treg balance. Overall, this research marks the first use of YPs to encapsulate two components, RH and EMO, presenting a promising therapeutic strategy for UC.

The Raman Active Vibrational Modes of Anthraquinones.

Anthraquinones are a family of natural products with useful bioactivity and optical properties. An anthraquinone called parietin is produced by extremophiles to protect against solar ultraviolet B radiation, so it is a potential biosignature in astrobiology. Raman spectroscopy, which is now used in space environments, can detect molecules such as parietin based on molecular vibrations. In this study, we show that time-dependent density functional theory (TDDFT) can accurately calculate the Raman spectra of three dihydroxyanthraquinones: parietin, emodin, and chrysophanol. By comparing calculated spectra to measured Raman spectra from purified powders, 10 vibrational modes are identified. The detailed molecular motions of these fused ring vibrations are described, and vibrations modes that are common to all three molecules are highlighted. In addition to powder spectra, Raman measurements from the thallus of Xanthoria parietina, a lichen that produces parietin, are reported, with excellent agreement to both the parietin powder and calculated Raman spectra. These results show that TDDFT calculations could make significant contributions to spectral analysis in the search for biotic organic materials beyond Earth.

Integrating Network Pharmacology and Experimental Verification to Explore the Pharmacological Mechanisms of Aloin Against Gastric Cancer.

Purpose: This study was designed to evaluate the pharmacological mechanisms of Aloin against gastric cancer (GC) via network pharmacology analysis combined with experimental verification. Methods: Using network pharmacology methods, the potential targets of Aloin and targets related to GC were screened from public databases. The protein-protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to predict the core targets and pathways of Aloin against GC. The expressions of major targets predicted by network pharmacology in normal stomach tissues and GC tissues and their relationships with overall survival of GC were searched in GEPIA, HPA and DriverDBv3 database. The results of network pharmacology analysis were verified by in vitro experiments. Results: A total of 129 potential targets were retrieved by searching the intersection of Aloin and GC targets. PPI network analysis indicated that 10 targets, including AKT1 and CASP3, were hub genes. GO enrichment analysis involved 93 biological processes, 19 cellular components, and 37 molecular functions. KEGG enrichment analysis indicated that the anti-cancer effect of Aloin was mediated through multiple pathways, such as PI3K-AKT, FoxO and Ras signaling pathway. Among them, the PI3K-AKT signaling pathway, which contained the largest number of enriched genes, may play a greater role in the treatment of GC. The validation of key targets in GEPIA, HPA and DriverDBv3 database showed that the verification results for most core genes were consistent with this study. Then, the results of in vitro experiment indicated that Aloin could inhibit proliferation of NCI-N87 cells and induce cell apoptosis. The results also showed that Aloin could decrease the mRNA and protein expressions of PI3K and AKT, suggesting that Aloin can treat GC by inducing cell apoptosis and regulating the PI3K-AKT signaling pathway. Conclusion: This study identified the potential targets of Aloin against GC using network pharmacology and in vitro verification, which provided a new understanding of the pharmacological mechanisms of Aloin in treatment of GC.

Aloin isoforms (A and B) selectively inhibits proteolytic and deubiquitinating activity of papain like protease (PLpro) of SARS-CoV-2 in vitro.

The most common host entry point of human adapted coronaviruses (CoV) including SARS-CoV-2 is through the initial colonization in the nostril and mouth region which is responsible for spread of the infection. Most recent studies suggest that the commercially available oral and nasal rinse products are effective in inhibiting the viral replication. However, the anti-viral mechanism of the active ingredients present in the oral rinses have not been studied. In the present study, we have assessed in vitro enzymatic inhibitory activity of active ingredients in the oral mouth rinse products: aloin A and B, chlorhexidine, eucalyptol, hexetidine, menthol, triclosan, methyl salicylate, sodium fluoride and povidone, against two important proteases of SARS-CoV-2 PLpro and 3CLpro. Our results indicate only aloin A and B effectively inhibited proteolytic activity of PLpro with an IC50 of 13.16 and 16.08 µM. Interestingly, neither of the aloin isoforms inhibited 3CLpro enzymatic activity. Computational structural modelling of aloin A and B interaction with PLpro revealed that, both aloin isoforms form hydrogen bond with Tyr268 of PLpro, which is critical for their proteolytic activity. Furthermore, 100 ns molecular dynamics (MD) simulation studies predicted that both aloin isoforms have strong interaction with Glu167, which is required for PLpro deubiquitination activity. Our results from the in vitro deubiquitinase inhibition assay show that aloin A and B isomers exhibit deubiquitination inhibitory activity with an IC50 value of 15.68 and 17.51 µM, respectively. In conclusion, the isoforms of aloin inhibit both proteolytic and the deubiquitinating activity of SARS-CoV-2 PLpro, suggesting potential in inhibiting the replication of SARS-CoV-2 virus.

Pharmacokinetics and metabolism of trans-emodin dianthrones in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum multiflorum Thunb. (PM) is a common traditional Chinese medicine with diverse biological activities of resolving toxins, nourishing livers and promoting hairs. Nevertheless, in recent years hepatotoxic adverse reactions caused by the administration of PM have raised worldwide concerns. In our previous study, we found that emodin dianthrones showed hepatotoxicity and may be potential toxicity markers. However, the metabolic transformation and pharmacokinetic behavior of emodin dianthrones in vivo have still not been elucidated. AIM OF THE STUDY: Taking trans-emodin dianthrones (TED) as an example, the present study was conducted to investigate the pharmacokinetics and bioavailability of TED in rats and characterized its metabolic transformation in the plasma, urine and feces of rats. MATERIALS AND METHODS: A rapid and sensitive UPLC-qqq-MS/MS method was developed for accurate quantification of TED in plasma and successfully applied to the pharmacokinetic evaluation of TED in rats after intravenous and oral administration. A reliable UFLC-Q-TOF-MS high resolution mass spectrometry combined with a scientific metabolite identification strategy was used to comprehensively characterize the metabolic transformation of TED in plasma, urine and feces in rats. RESULTS: The established UPLC-qqq-MS/MS method had a linear range of 1-500 ng/mL, and the method was accurate and reliable to meet the quantitative requirements. When 20 mg/kg TED was given by gavage rats, it was rapidly absorbed into the circulatory system and had a long half-life time of 6.44 h and wide tissue distribution in vivo. While intravenous injection of 0.4 mg/kg TED in rats, it was rapidly metabolized and eliminated with a half-life time of 1.82 h. The oral absorption bioavailability of TED was only 2.83%. Furthermore with a sensitive UFLC-Q-TOF-MS technique and metabolite identification strategy, 21 metabolites were successfully identified, including 11 in plasma, 12 in urine and 18 in feces. The main Ⅰ and Ⅱ phase metabolic processes involved glucuronidation, oxidation, carbonylation, (de)methylation, sulfation and hydrogenation. CONCLUSION: TED could be rapidly absorbed into the blood circulation and widely distributed and slowly metabolized in the body and underwent extensive cleavage and metabolic transformation in vivo. The study provided a basis for in-depth elucidation of the toxicology and mechanism research of TED, but also laid the foundation for further research on the material basis of hepatotoxicity of PM.

In Vitro Anticancer Screening and Preliminary Mechanistic Study of A-Ring Substituted Anthraquinone Derivatives.

Anthraquinone derivatives exhibit various biological activities, e.g., antifungal, antibacterial and in vitro antiviral activities. They are naturally produced in many fungal and plant families such as Rhamnaceae or Fabaceae. Furthermore, they were found to have anticancer activity, exemplified by mitoxantrone and pixantrone, and many are well known redox-active compounds. In this study, various nature inspired synthetic anthraquinone derivatives were tested against colon, prostate, liver and cervical cancer cell lines. Most of the compounds exhibit anticancer effects against all cell lines, therefore the compounds were further studied to determine their IC50-values. Of these compounds, 1,4-bis(benzyloxy)-2,3-bis(hydroxymethyl)anthracene-9,10-dione (4) exhibited the highest cytotoxicity against PC3 cells and was chosen for a deeper look into its mechanism of action. Based on flow cytometry, the compound was proven to induce apoptosis through the activation of caspases and to demolish the ROS/RNS and NO equilibrium in the PC3 cell line. It trapped cells in the G2/M phase. Western blotting was performed for several proteins related to the effects observed. Compound 4 enhanced the production of PARP and caspase-3. Moreover, it activated the conversion of LC3A/B-I to LC3A/B-II showing that also autophagy plays a role in its mechanism of action, and it caused the phosphorylation of p70 s6 kinase.

Cysteine-Based Protein Covalent Binding and Hepatotoxicity Induced by Emodin.

Emodin (EMD) is a major ingredient of Polygonum multiflorum Thunb. (PMT), which has shown adverse liver reactions. Despite multiple pharmacological activities, EMD is reported to show various toxicities. Our early study demonstrated the reactivity of EMD to glutathione. This study aimed to determine the covalent interaction of hepatic protein with EMD and the correlation of the protein modification with hepatotoxicity induced by EMD. EMD-derived protein adduction was detected in an incubation mixture containing mouse liver homogenates and EMD. Such protein adduction was also observed in hepatic protein obtained from mice exposed to EMD. The protein covalent binding occurred in time- and dose-dependent manners. Pre-treatment of l-buthionine-sulfoximine significantly potentiated EMD-induced adduction and hepatotoxicity caused by EMD and lipopolysaccharide co-treatment. As expected, EMD-derived protein modification was observed in mouse primary hepatocytes treated with EMD. The increase in EMD exposure concentration intensified EMD-derived protein adduction and increased EMD-induced cell death. The susceptibility of hepatocytes to EMD cytotoxicity and the intensity of EMD-induced protein adduction were attenuated by the co-treatment of hepatocytes with N-acetyl cysteine. A good association of protein modification with hepatotoxicity induced by EMD was illustrated, which facilitates the understanding of the mechanism of hepatotoxicity induced by EMD.

Physcion, a novel inhibitor of 5α-reductase that promotes hair growth in vitro and in vivo.

Androgenic alopecia (AGA) has a high incidence. Excess dihydrotestosterone in blood capillaries, which is converted from testosterone by 5α-reductase, is an AGA causative factor. We identified the inhibitory activity of four Polygonum multiflorum compounds against 5α-reductase via high-performance liquid chromatography, and the results showed that Physcion was a potent 5α-reductase inhibitor. Additionally, we found that through inhibiting 5α-reductase expression, Physcion could shorten the time of dorsal skin darkening and hair growth, improve hair follicle morphology, and significantly increase hair follicle count. Eventually, through molecular docking study, we found the binding energy and molecular interactions between Physcion and 5α-reductase type II. These results suggested that Physcion is a potent 5α-reductase inhibitor, as well as a new natural medicine for treating AGA.

Aloe-emodin derivative produces anti-atherosclerosis effect by reinforcing AMBRA1-mediated endothelial autophagy.

Atherosclerosis is an inflammatory disease of high lethality associated with endothelial dysfunction. Due to the pathophysiological complexity and our incomplete understanding of the mechanisms for the development and progression of atherosclerosis, effective means for the prevention and treatment of atherosclerosis still need further exploration. This study was designed to investigate the potential effects and underlying mechanisms of aloe-emodin derivative (AED) on atherosclerosis. High fat diet (HFD) treated ApoE-/- mice were used as an animal model of atherosclerosis. Intragastric administration of aloe-emodin (AE) or AED for 12 weeks markedly reduced the atherosclerotic plaque in aorta with decreased plaque area, lipid accumulation, macrophage infiltration, collagen content and metabolic abnormalities. By comparison, AED produced more potent anti-atherosclerosis effects than AE at the same dose. AED enhanced production of autophagy flux in cultured human aortic endothelial cells (HAECs). Moreover, AED increased the expression of activating molecule in Beclin1-regulated autophagy 1 (AMBRA1), a key protein involved in autophagosome formation. Furthermore, knockdown of AMBRA1 blocked the promotion effect of AED on autophagy in HAECs. Taken together, AED facilitates endothelial autophagy via AMBRA1 during the progression of atherosclerosis, suggesting the potential application of this compound for atherosclerosis treatment.

Photosensitization of a subcutaneous tumour by the natural anthraquinone parietin and blue light.

Photodynamic therapy (PDT) is an anticancer treatment involving administration of a tumour-localizing photosensitizer, followed by activation by light of a suitable wavelength. In previous work, we showed that the natural anthraquinone (AQ) Parietin (PTN), was a promising photosensitizer for photodynamic therapy of leukemic cells in vitro. The present work aimed to analyze the photosensitizing ability of PTN in the mammary carcinoma LM2 cells in vitro and in vivo in a model of subcutaneously implanted tumours. Photodynamic therapy mediated by parietin (PTN-PDT) (PTN 30 µM, 1 h and 1.78 J/cm2 of blue light) impaired cell growth and migration of LM2 cells in vitro. PTN per se induced a significant decrease in cell migration, and it was even more marked after illumination (migration index was 0.65 for PTN and 0.30 for PTN-PDT, *p < 0.0001, ANOVA test followed by Tukey's multiple comparisons test), suggesting that both PTN and PTN-PDT would be potential inhibitors of metastasis. Fluorescence microscopy observation indicated cytoplasmic localization of the AQ and no fluorescence at all was recorded in the nuclei. When PTN (1.96 mg) dissolved in dimethyl sulfoxide was topically applied on the skin of mice subcutaneously implanted with LM2 cells, PTN orange fluorescence was strongly noticed in the stratum corneum and also in the inner layers of the tumour up to approximately 5 mm. After illumination with 12.74 J/cm2 of blue light, one PDT dose at day 1, induced a significant tumour growth delay at day 3, which was not maintained in time. Therefore, we administered a second PTN-PDT boost on day 3. Under these conditions, the delay of tumour growth was 28% both on days 3 and 4 of the experiment (*p < 0.05 control vs. PTN-PDT, two-way ANOVA, followed by Sidak's multiple comparisons test). Histology of tumours revealed massive tumour necrosis up to 4 mm of depth. Intriguingly, a superficial area of viable tumour in the 1 mm superficial area, and a quite conserved intact skin was evidenced. We hypothesize that this may be due to PTN aggregation in contact with the skin and tumour milieu of the most superficial tumour layers, thus avoiding its photochemical properties. On the other hand, normal skin treated with PTN-PDT exhibited slight histological changes. These preliminary findings encourage further studies of natural AQs administered in different vehicles, for topical treatment of cutaneous malignancies.

ß-1,3-d-Glucan based yeast cell wall system loaded emodin with dual-targeting layers for ulcerative colitis treatment.

Herein, a ß-1,3-d-glucan based microcarrier, yeast cell wall microparticles (YPs), was used to develop a food-source-based nano-in-micro oral delivery system for ulcerative colitis (UC) treatment. Briefly, lactoferrin (Lf), which targets intestinal epithelial cells, was used to encapsulate emodin (EMO) to form nanoparticles (EMO-NPs), and then loaded into YPs with the natural macrophages targeting ability, forming a final formula with two outer-inner targeting layers (EMO-NYPs). These dual-targeting strategy could enhance the dual-effects of EMO in anti-inflammatory and mucosal repair effects respectively. As expected, cell uptake assessment confirmed that EMO-NPs and EMO-NYPs could target on the Lf and dection-1 receptors on the membranes of Caco-2 cells and macrophages, respectively. Importantly, EMO-NYPs showed the best anti-UC effects compared to EMO-NPs and free EMO, by inhibiting NF-κB pathway to anti-inflammation and promoting intestinal mucosa repair via MLCK/pMLC2 pathway. The results show that EMO-NYPs are a promising food-based oral delivery system in anti-UC.

The Health Benefits of Emodin, a Natural Anthraquinone Derived from Rhubarb-A Summary Update.

Emodin (6-methyl-1,3,8-trihydroxyanthraquinone) is a naturally occurring anthraquinone derivative found in roots and leaves of various plants, fungi and lichens. For a long time it has been used in traditional Chinese medicine as an active ingredient in herbs. Among other sources, it is isolated from the rhubarb Rheum palmatum or tuber fleece-flower Polygonam multiflorum. Emodin has a wide range of biological activities, including diuretic, antibacterial, antiulcer, anti-inflammatory, anticancer and antinociceptive. According to the most recent studies, emodin acts as an antimalarial and antiallergic agent, and can also reverse resistance to chemotherapy. In the present work the potential therapeutic role of emodin in treatment of inflammatory diseases, cancers and microbial infections is analysed.